Diabetes mellitus is a chronic disease and one of the major public health problems of our time. Worldwide there is an ever increasing population of patients with diabetes that are imposing a major financial burden on health systems. The prevalence of diabetes for all age-groups worldwide was estimated to be 2.8% in 2000 and 4.4% by 2030. The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030. In 2002 the prevalence of diabetes in the Australian population was 7.4% in those 25 years and older, and the number of Australians with diabetes has trebled since 1981.
Type 2 diabetes is by far the most common, e.g. affecting 90 to 95% of the U.S. diabetes population. Diabetes mellitus prevalence increases with age, and the numbers of older persons with diabetes are expected to grow as the elderly population increases in number. Along with the rising rate of diabetes there is also a higher prevalence of impaired glucose metabolism, which is associated with an increased risk of heart disease and diabetes. Diabesity is a term which encompasses the prevalence of diabetes, obesity, impaired glucose metabolism and the associated risk factors of hypertension and abnormal plasma lipid profiles (dyslipideamia). The “diabetes epidemic” will continue even if levels of obesity remain constant. Given the increasing prevalence of obesity, it is likely that these figures underestimate future diabetes prevalence.
Diabetes mellitus is a condition where the body cannot maintain normal blood glucose levels. Most cases of diabetes mellitus fall into three broad categories: Type 1, Type 2 and gestational diabetes. Type 1 diabetes results from the body's failure to produce insulin, and presently requires the person to inject insulin. Type 2 diabetes results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency.
Type 2 diabetes can usually be controlled in the first instance by regular exercise and diet. Tablets and eventually insulin injections may be needed as the disease progresses. Over time, high blood glucose levels may damage blood vessels and nerves. These complications of diabetes can cause damage to eyes, nerves and kidneys and increase the risk of heart attack, stroke, impotence and foot problems. This damage can happen before an individual knows that they have diabetes if left undetected for a long time. Therefore, it is important to diagnose and control diabetes and its complications at a very early stage.
Diabetes is also the largest cause of kidney disease (nephropathy) in developed countries and is accountable for huge costs in dialysis. 10% to 20% of people with diabetes will die of kidney (renal) failure. The reasons behind the complication of nephropathy in diabetes is complex, and includes the toxic effects of high glucose levels; elevated blood pressure; abnormal lipid levels and abnormalities of small blood vessels. The accumulative result is that there is thickening of the glomeruli in the kidney which allows protein (albumin) to be excreted in the urine.
Diabetes has become the single most common cause of end stage renal failure (ESRF) at 40-50% of ESRD cases and annual Australian Medicare expenditures are greatest for patients with ESRF caused by diabetes compared with all other primary ESRD diagnoses. Up to one-third of adults with newly diagnosed type 2 diabetes already have chronic renal disease, and data suggest that in many of these patients it may have developed in the course of the pre-diabetic state. The disease is progressive and affects more men than women.
Diabetic nephropathy is detected primarily by measuring the amount of albumin excreted in the urine (albuminuria). Albuminuria is usually measured using the albumin creatinine ratio (ACR). This is the ratio between the albumin and the creatinine in the urine. The ratio considers the concentration of the albumin in relation to the glomerular filtration rate, which is determined by the amount of creatinine in the urine. Albuminuria is defined as: ACR >2.5 mg/mmol (men) or >3.5 mg/mmol (women).
Despite numerous studies and algorithms that have been used to assess the risk of Diabetes and related conditions, there remains a need for accurate methods of assessing such risks or conditions that can be readily adopted by primary care physicians who are most likely to initially encounter the pre-diabetic or undiagnosed early diabetic.
Accordingly, there remains a need for relatively inexpensive and convenient methods for screening persons at risk for developing pre-Diabetes, Diabetes and/or a Diabetes related condition and for monitoring patients with pre-Diabetes, Diabetes and/or a Diabetes related condition. Such methods could be used for screening a large population to identify persons at risk for Diabetes, for testing a single person to determine that individual's risk of developing Diabetes, for monitoring the health of diabetes patients and assessing the efficacy of interventions designed to treat Diabetes, pre-Diabetes and/or related conditions. There is also a need to identify new drug targets for pre-Diabetes, Diabetes and/or Diabetes related conditions including protein drug targets. Identification of new drug targets will enable the development of new interventions for pre-Diabetes, Diabetes and/or Diabetes related conditions.
It is against this background and the problems and difficulties associated therewith that the present invention has been developed.